Elevated interleukin-10: A new cause of dyslipidemia leading to severe HDL deficiency

The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

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“…The lipid levels in this child correlated with disease activity and improved with therapy as has been reported by other groups [4, 5]. …”

Section: Discussionsupporting

confidence: 84%

Autoimmune Lymphoproliferative Syndrome: A Rare Cause of Disappearing HDL Syndrome

Sriram

Joshi

Rodriguez

et al. 2016

Case Reports in Immunology

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“…This may feed in to immune aberrations given the important role of vitamin D in promoting the generation of regulatory T cells [39]. However, interleukin-10, usually seen as an anti-inflammatory cytokine produced by regulatory T cells, has been shown to induce a precipitous decline in HDLc when administered to patients [40], and so it seems likely that the inflammatory cytokine milieu of rheumatoid arthritis is complex but may be driving the lipid and metabolic changes.…”

Section: Lipids In Ramentioning

confidence: 99%

Lipid and Metabolic Changes in Rheumatoid Arthritis

McGrath

Young

2015

Curr Rheumatol Rep

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While the most obvious manifestations of rheumatoid arthritis (RA) involve inflammation and damage in the synovial joints, the systemic effects of the condition are widespread and life-threatening. Of particular interest is the 'lipid paradox' of RA, where patients with a numerically equivocal starting lipid profile have a significantly raised risk of cardiovascular (CV) events and response to therapy results in a 'normalization' of lipid levels and reduction in events. Changes in lipids can be seen before overt disease manifestations which suggest that they are closely linked to the more widespread inflammation-driven metabolic changes associated with tumour necrosis factor (TNF). Cachexia involves a shift in body mass from muscle to fat, which may or may not directly increase the cardiovascular risk. However, since TNF inhibition is associated with reduction in cardiovascular events, it does suggest that these widespread metabolic changes involving lipids are of importance. Analysis of single lipids or metabolites have been used to identify some of the key changes, but more recently, metabolomic and lipidomic approaches have been applied to identify a broad spectrum of small molecule changes and identify potentially altered metabolic pathways. Further work is needed to understand fully the metabolic changes in lipid profiles and identify novel ways of targeting desired profile changes, but work so far does suggest that a better understanding may allow management of patients to downregulate the systemic effects of their disease that puts them at risk of cardiovascular complications.

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“…Known acquired causes for low and possibly very low HDL-C include some malignancies, severe sepsis, and other systemic illnesses that cause increased interleukin (IL)-10, and certain drugs, including anabolic steroids, fibrates, and thiazolidinediones (2,4,5 ). None of these applied to the patient under discussion, except perhaps for the possibility of increased IL-10 production as discussed in the next paragraph.…”

Section: Discussionmentioning

confidence: 99%